Oncologists have historically been limited to utilizing clinical features such as histopathology and staging information to guide treatment decisions. Although this has been a practical and fruitful approach for decades, it is clear that even among patients with similar clinical cancer features, heterogeneity in response to treatment and outcomes exist. The paradigm of more precision therapy in cancer began to evolve with the identification and targeting of driver mutations and a more personalized approach to treatment became possible.1, 2, 3, 4, 5 As efficient and affordable next-generation sequencing (NGS) has become available, more personalized approaches to oncologic therapy have garnered considerable excitement and become increasingly utilized6.

Most of the advancements within precision oncology currently in clinical practice have been in relation to systemic therapy. Within the field of radiation oncology, advancements in precision of treatments have predominately been with respect to improvements in localization7, 8, 9, 10 and conformality.11, 12, 13, 14 Dosing and fractionation however, is still largely determined by histology and extent of disease (macroscopic vs microscopic) while maintaining safety to relevant organs at risk. Several clinical trials in various disease sites have evaluated dose escalation/de-escalation strategies in an effort to identify the optimal therapy to balance tumor control with toxicity. Although this has allowed for a general identification of safe and therapeutic doses, it is evident from clinical outcomes there is significant heterogeneity within patients with matched tumor type and stage.

Gaining a better understanding of the prognostic and predictive value molecular alterations may allow for greater personalization of radiation tailored to the radiosensitivity of a specific tumor. The genomic adjusted radiation dose/radiosensitivity index15,16 is one such emerging focus of study that holds promise to improve precision radiation dosing with a pan-cancer approach and is the subject of a separate review within this special issue. Herein, we review current select literature of histology specific molecular biomarkers that may guide precision radiotherapy (RT) with a greater focus on breast and prostate cancer due to the presence of commercially available and prospectively validated biomarkers.